Nitrous oxide containing dermatological composition

ABSTRACT

Dermatological compositions comprising nitrous oxide and at least one essential fatty acid or lower alkyl ester thereof in a dermatologically acceptable carrier medium is useful in the treatment of a variety of skin, muscle and joint disorders including psoriasis, shingles, fever blisters, chicken pox, ache, chilblains, eczema, chloasmas, alopecia, dermatitis, ringworm and burn wounds. The composition preferably also includes additional ingredients selected from coal tar, collagen, nicotinamide, nicotinic acid, lanolin, vitamin E, methyl salicylate, arnica, and H 1  -antagonist antihistamines or combinations thereof.

FIELD OF THE INVENTION

This invention relates to dermatological compositions. The compositionsof this invention are suitable to be applied to the human skin for thetreatment of a variety of skin, muscular, joint and peripheralcirculatory conditions.

BACKGROUND OF THE INVENTION

It is known in the field of dermatology to make use of coal tarpreparations in the treatment of certain skin conditions, for example,psoriasis [Hunter J. A. A., Savin J. A. and Dahl M. V., ClinicalDermatology, Blackwell Scientific Publications p.49].

It has also been suggested that essential fatty acids, including eveningprimrose oil may be used in the treatment of skin conditions such aseczema [see references cited by July Graham, Evening Primrose Oil,Thorsons, pp. 127-128].

Various other compositions are known to be used in the treatment ofthese and other skin conditions.

OBJECT OF THE INVENTION

It is an object of the present invention to provide novel dermatologlcalcompositions.

SUMMARY OF THE INVENTION

According to the present invention there is provided a dermatologicalcomposition having as active ingredients nitrous oxide and at least oneessential fatty acid or ester thereof selected from the group consistingof linoleic acid, arachidonic acid, linolenic acid, gamma-linolenicacid, and the lower alkyl esters thereof in a dermatologicallyacceptable carrier.

The composition may further include one or more supplementaryingredients selected from the group consisting of Liquor Picis Carbonis[also known as coal tar solution], collagen, nicotinamide, nicotinicacid, lanolin, vitamin E, methyl salicylate, and known H₁ -antagonistantihistamines.

In the preferred form of the invention the composition is saturated withnitrous oxide.

Also in the preferred form of the invention the essential fatty acidcomponent of the composition comprises a mixture of esters of the fattyacids listed above. Thus in the most preferred form of the invention thefatty acid component of the composition is constituted by the complexknown as Vitamin F and in this regard it is preferred to make use of theester form of Vitamin F known as Vitamin F Ethyl Ester. This product iscommercially available under the trade description of Vitamin F EthylEster CLR 110 000 Sh.L. U./g from CLR Chemicals Laboratorium Dr. KurtRichter GmbH, of Berlin, Germany. The typical fatty acid distribution ofthis product is as follows:

    ______________________________________                                               <C.sub.16      0%                                                             C.sub.16-0     8,3%                                                           C.sub.18-0     3,5%                                                           C.sub.18-1     21,7%                                                          C.sub.18-2     34,8%                                                          C.sub.18-3     28,0%                                                          >C.sub.18      1,6%                                                           unknown        2,1%                                                    ______________________________________                                    

In one preferred form of the invention the composition comprises onlycoal tar solution as a supplementary active ingredient. In this form ofthe invention the composition is useful in the treatment of psoriasis,fever blisters, herpes simplex, shingles, chicken pox and eczematousconditions of the skin and scalp.

In another form of the invention the composition comprises coal tarsolution in combination with one of collagen, nicotinamide, and lanolin.In these forms of the invention the composition has been shown to beuseful for the treatment of ache, conditions involving poor peripheralcirculation, such as chilblains, and uhthyoses respectively.

In an alternative form of the invention the composition may contain coaltar solution in combination with an antihistamine selected from the H₁-antagonist group and be used for the treatment of atopic and allergicconditions manifesting in skin irritations, such as eczema, dermatitisand ringworm.

In a further form of the invention the supplementary ingredient maycomprise methyl salicylate in which form the composition is useful inthe treatment of muscle and joint pains.

The composition may finally comprise collagen and lanolin assupplementary ingredients in which form it is useful in cosmeticpreparations, or for the treatment of alopecia or minor skin ailments,such as chloasmas.

The composition may be formulated to have any dermatologicallyacceptable consistency, i.e. as a lotion, cream, ointment or gel.

EXAMPLES OF THE INVENTION

Without thereby limiting the scope of the invention some examples willnow be described to illustrate the invention.

EXAMPLE 1

Dermatological composition useful in treatment of psoriasis

Five liters of water was saturated with N₂ O at room temperature in apressure vessel. 75 g of vitamin F ethyl ester, 50 g vitamin E and 50 gchremaphor was mixed and heated to about 80° C. and the mixture wasemulsified in the N₂ O saturated water with stirring. 500 ml of aprepared coal tar solution BP73 [also known as Liquor Picis Carbonis]was produced by dissolving 100 g of prepared coal tar BP73 in 375 g ofethyl alcohol with the addition of Polysorbate 80. The coal tar solutionwas saturated with N₂ O in a pressure vessel and mixed with the aboveemulsion. The viscosity of the solution was modified according totechnique known in the trade i.e. with xanthan gum to provide a gel. Inthis regard it is preferred to use Keltrol ® TF, a product marketedcommercially by the Kelco Division of Merck & Co., Inc. If desired asuitable preservative such as a parabenz compound may be added.

The resulting gel was used in the treatment of 53 psoriasis sufferers.All these sufferers had previously attempted alternative forms ofpsoriasis medication and treatment and without success. Such treatmentsincluded UV radiation, coal tar, cortizone and etretinate preparationsand even Dead Sea baths. The patients applied the gel as described aboveto the affected areas 2 or 3 times daily. Of those treated 88.7%reported a definite improvement in their condition. On average theperiod of treatment before positive results were seen was 3 weeks. In 6%of the cases it took more than 6 weeks of treatment before improvementswere seen. 72% of the patients treated were considered to have derivedlong term results from the use of the gel described above as evidencedby the clearing and sustained absence of lesions for a period of morethan 3 months. Such long term results were achieved on average after 8.5weeks of treatment. In treating patients with a gel it is preferred touse a suitable skin moisturiser with the gel to prevent drying out ofthe skin. Such moisturising ingredients may of course also beincorporated into the composition of the invention to produce a creamformulation which may then be used as a supplementary treatment with thegel formulation.

EXAMPLE 2

Alternative dermatological composition for use in treatment of psoriasisand fever blisters [Herpes Simplex infection] and eczematous skinconditions

An alternative dermatological composition was made up to contain thefollowing ingredients in the quantities stated per 100 g of finalproduct:

    ______________________________________                                                              gram                                                    ______________________________________                                        Prepared coal tar BP1973                                                                              1,00                                                  Vitamine F Ethyl Ester  1,50                                                  Nitrous Oxide [N.sub.2 O]                                                                             qs                                                    Polysorbate 80 [emulsifier]                                                                           0,25                                                  Ethyl Alcohol [solvent/dispersant]                                                                    3,75                                                  PEG-40 [Hydrogenated caster oil - as                                                                  0,45                                                  solubilizer]                                                                  Vitamine E [dl-alpha Tocopherol - as                                                                  0,30                                                  antioxidant]                                                                  Sodium propyl paraben [as preservative]                                                               0,05                                                  Methyl paraben [as preservative]                                                                      0,10                                                  Xanthan Gum             0,8-0.9                                               Water                   balance                                                                       100                                                   ______________________________________                                    

The coal tar and polysorbate 80 [Criliet 4] were mixed with warming torender it fluid and poured into about 75% of the ethyl alcohol withstirring which was continued for 1 hour to achieve dispersion. Themixture was allowed to cool for 24 hours, the supernatant was decantedthrough a filter and the mixing vessel and filter were washed with partof the remaining alcohol added thereto. The resulting solution wascharged with N₂ O gas by maintaining the solution in a pressure vesselunder N₂ O at 2 bar for 96 hours. The N₂ O charged coal tar solution wasstored in a cool place.

The water fraction of the composition was prepared by charging the waterwith N₂ O for 48 hours at 2 bar as described above. Again, the N₂ Ocharged water was kept in a cool place.

A Third sub-mixture was prepared by mixing together and heating to 80°C. the Vitamin F, Vitamin E and PEG-40 hydrogenated castor oil. Oncemixed the methyl paraben was added with stirring to obtain a homogenousmixture of oil miscible fractions. This mixture was kept at 80° C. andadded with stirring into part of the N₂ O charged water which hadpreviously been prepared and provided with the sodium propyl paraben toproduce an oil-in-water emulsion.

Finally, the balance of the N₂ O charged water, the charged coal tarsolution and the oil-in-water emulsion were mixed with stirring whilegranulated xanthan gum was slowly added to the mixture in sufficientquantity to achieve a viscosity of 1740 cps.

The gel is passed through a 60 mesh sieve and packaged into scalablecontainers.

The gel formulated as set out adore is presently undergoing double blindcrossover clinical trials against aqueous cream as placebo for thetreatment of fever blisters [Herpes Simplex infection]. It is expectedthat the results will confirm earlier results obtained in uncontrolledtrials in which the composition was found effective against suchinfections as well as to provide relief to patients suffering fromshingles, chicken pox, psoriasis and eczematous conditions of the skin.

EXAMPLE 3

Dermatological composition for use in the treatment of eczema anddermatitis

A composition having the components as set out in Example 2 but with theaddition of 1 g diphenhydramine hydrochlorlde and made up as thereindescribed was found in uncontrolled trials to bring relief and remissionto patients suffering from atopic eczema as well as to patientssuffering from dermatits.

EXAMPLE 4

Composition for treatment of chilblains

A composition as described in Example 2 to which 1 g of nicotinic acidhad been added was reported by patients to relieve the symptoms ofchilblains and to restore healthy skin.

EXAMPLE 5

Composition for treatment of acne and scar tissue

A composition as described in Example 2 was made up with the furtheraddition of 1.5 g collagen and 1.5 g lanolin.

This composition was successfully tested on persons suffering from achevulgaris and was found not only to clear up the condition but also toresult in visual improvement of appearance of the formerly heavilyblemished skin.

The same composition was also used by a 13 year old patient some oneyear after she had suffered extensive third degree burn wounds on theface, shoulders and back. Encouraging signs of repair of the scarredskin was observed.

EXAMPLE 6

Composition for treatment of fibrositis, muscle cramps, and improvementof peripheral circulation

A composition as described in Example 2 but not including coal tar,polysorbate 80 and alcohol was made up substantially as thereindescribed. This composition was found in several trials to givesubstantial relief of fibrositis and muscular cramps when topicallyapplied. It was also reported by patients to relieve swelling followingtissue trauma such as caused by bumps or falls giving rise to impairedblood circulation. Some patients found that the effect of thiscomposition was enhanced after the addition thereto of methyl silicateor arnica.

EXAMPLE 7 Cosmetic Composition

A composition as described in Example 2 but omitting the coal tar,polysorbate 80 and alcohol and with the addition of 1.5 g collagen. 1.5g lanolin and 1.5 g additional Vitamin E resulted in a cosmetic productwhich was found to be suitable for the removal of chloasmas, warts andmoles and which also stimulated hair growth in alopecia cases.

Many variations of the invention may be devised without departing fromthe scope and spirit of the invention.

I claim:
 1. A topical composition, comprising as active ingredients,nitrous oxide and at least one essential fatty acid or lower alkyl esterthereof, selected from the group consisting of linoleic acid,arachidonic acid, linolenic acid and gamma-linolenic acid, incombination with a dermatologically acceptable carrier.
 2. A topicalcomposition according to claim 1, further comprising at least onesupplementary active ingredient selected from the group consisting ofcoal tar solution, collagen, nicotinamide, nicotinic acid, lanolin,vitamin E, methyl salicylate, and an H₁ -antagonist antihistamine.
 3. Atopical composition according to claim 2, wherein the composition issaturated with nitrous oxide.
 4. A topical composition according toclaim 1, wherein the at least one essential fatty acid or lower alkylester thereof comprises a mixture of esters of the fatty acids set outtherein.
 5. A composition according to claim 1, wherein the at least oneessential fatty acid or lower alkyl ester thereof is Vitamin F EthylEster.
 6. A composition according to claim 2, wherein the at least onesupplementary active ingredient is coal tar solution.
 7. A compositionaccording to claim 2, wherein the at least one supplementary activeingredient is coal tar solution and a second supplementary activeingredient selected from the group consisting of collagen, nicotinamideand lanolin.
 8. A composition according to claim 2, wherein the at leastone supplementary active ingredient is coal tar solution and an H₁-antagonist antihistamine.
 9. A composition according to claim 2,wherein the at least one supplementary active ingredient is methylsalicylate.
 10. A composition according to claim 2, wherein the at leastone supplementary active ingredient is collagen and lanolin.
 11. Amethod of treating a condition selected from the group consisting ofskin, muscular, joint and peripheral circulatory condition in a patientin need of such treatment, comprising applying topically to the skin ofthe patient a condition-treating effective amount of a topicalcomposition according to claim
 1. 12. A composition according to claim1, further comprising coal tar solution as a supplementary activeingredient.
 13. A composition according to claim 1, wherein the at leastone essential fatty acid or lower alkyl ester thereof is Vitamin F EthylEster, and the composition further comprises coal tar solution as asupplementary active ingredient.